Identification of actin network proteins, talin-1 and filamin-A, in circulating extracellular vesicles as blood biomarkers for human myalgic encephalomyelitis/chronic fatigue syndrome

Brain Behav Immun. 2020 Feb;84:106-114. doi: 10.1016/j.bbi.2019.11.015. Epub 2019 Nov 20.

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, debilitating disorder with a wide spectrum of symptoms, including pain, depression, and neurocognitive deterioration. Over 17 million people around the world have ME/CFS, predominantly women with peak onset at 30-50 years. Given the wide spectrum of symptoms and unclear etiology, specific biomarkers for diagnosis and stratification of ME/CFS are lacking. Here we show that actin network proteins in circulating extracellular vesicles (EVs) offer specific non-invasive biomarkers for ME/CFS. We found that circulating EVs were significantly increased in ME/CFS patients correlating to C-reactive protein, as well as biological antioxidant potential. Area under the receiver operating characteristic curve for circulating EVs was 0.80, allowing correct diagnosis in 90-94% of ME/CFS cases. From two independent proteomic analyses using circulating EVs from ME/CFS, healthy controls, idiopathic chronic fatigue, and depression, proteins identified from ME/CFS patients are involved in focal adhesion, actin skeletal regulation, PI3K-Akt signaling pathway, and Epstein-Barr virus infection. In particular, talin-1, filamin-A, and 14-3-3 family proteins were the most abundant proteins, representing highly specific ME/CFS biomarkers. Our results identified circulating EV number and EV-specific proteins as novel biomarkers for diagnosing ME/CFS, providing important information on the pathogenic mechanisms of ME/CFS.

Keywords: Actin network proteins; Circulating EV; ME/CFS; Non-invasive biomarkers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins
  • Actins / metabolism*
  • Adult
  • Biomarkers / blood
  • Depression / blood
  • Extracellular Vesicles / metabolism*
  • Fatigue Syndrome, Chronic / blood*
  • Female
  • Filamins / blood*
  • Humans
  • Male
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proteomics
  • Talin / blood*

Substances

  • 14-3-3 Proteins
  • Actins
  • Biomarkers
  • Filamins
  • TLN1 protein, human
  • Talin